Is Metformin Safe? Global Health Agencies Investigating Link to NDMA

Over the past year, world regulatory agencies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have uncovered, investigated, and recalled medications due to nitrosamine impurities such as NDMA. In 2018, many of the blood pressure ‘sartan’ medications (angiotensin II receptor blockers known as ARBs), including Valsartan and Losartan, were recalled due to NDMA contamination. In 2019 and 2020, various companies have issued voluntary recalls of popular heartburn medication Zantac and other ranitidine products after uncovering NDMA contamination.

In December 2019, the global investigations of NDMA impurities extended to the type-2 diabetes drug Metformin after the public health agency of Singapore recalled three out of the 46 locally marketed Metformin medications due to the presence of NDMA.

Singapore Metformin Recalls

Singapore’s Health Sciences Authority (HSA) tested all 46 locally distributed Metformin medicines and three were found to have trace amounts of NDMA which were “above the internationally accepted level.”

As a result, on December 4, 2019 the HSA recalled the three medicines as a “precautionary measure” but also announced that the other 43 Metformin medications were not contaminated.

Which Metformin Medications were Recalled in Singapore?

  • One batch of Glucient XR Tablet 500mg—supplied by Glorious Dexa Singapore
  • All batches of Meijumet Prolonged Release Tablet in 750mg and 1000mg –supplied by Pharmazen Medical

Singapore’s HSA claims that the risk to patients who have been taking the affected medications is “very low” because the potential risks of nitrosamine contamination is associated with long-term use of the affected drugs, and the recalled medicines have only been sold in Singapore since 2018.

Have Any Other Government Health Agencies Recalled Metformin?type-2-diabetes-pills

Currently, only Singapore’s HSA has issued recalls for Metformin medications. However, as a result of the recalls, worldwide regulatory agencies such as the U.S. FDA, Health Canada, European Medicines Agency (EMA), and the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) have opened investigations into possible NDMA contamination in their Metformin medications.

In statements from the FDA, EMA, Health Canada, and MHRA, the agencies claim that there is no evidence that any Metformin medications distributed in their respective territories are affected and have advised patients to continue taking their medications.

U.S. FDA’s Metformin Investigation

The FDA reacted to Singapore’s Metformin recalls by announcing an investigation into potential NDMA impurities in Metformin available in the United States. Currently, no Metformin recalls have been issued by the FDA and no NDMA contamination has been found in lots sold in the United States.

Pertaining to the affected samples outside of the United States, the FDA claims that “based on the information we have available, the levels of NDMA seen outside the U.S. are within the range that is naturally occurring in some foods and in water.”

The investigation will determine whether there is NDMA in Metformin, and if so whether that amount is above the United States’ acceptable daily intake limit of 96 nanograms. The FDA “will recommend recalls as appropriate if high levels of NDMA are found,” according to a statement from Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research.

Dr. Woodcock recommends that U.S. patients should continue taking Metformin while the investigation continues to keep their diabetes under control because “there are no alternative medications that treat this condition in the same way.”

European Medicine Agency’s Metformin Investigation

The EMA—the drug advising department for the European Union—has partnered with companies manufacturing and distributing Metformin within the EU to test the medication for NDMA. The results have thus far found no data indicating that EU Metformin medicines have been affected and recommends that patients in the EU should continue taking Metformin as prescribed.

The EMA is aware of trace amounts of NDMA found in a small number of Metformin medications outside of the EU; however, the organization claims that the levels of NDMA found in affected non-EU Metformin medicines are very low and appear to be within or even below the range people can be exposed to from other sources including water and certain foods.

Health Canada’s Metformin Investigation

Health Canada has asked drug manufacturers and distributors of Metformin to “test their own Metformin products” and will be “collecting samples from those companies to conducts its own testing.”

After the investigation, Health Canada announced that it is not aware of any Metformin products available in Canada that contain NDMA above the acceptable limits; however, it is working closely with international regulatory agencies to continually assess the concerns.

What is Metformin?

Metformin is a prescription medication available in both generic and brand name forms that helps those suffering from type 2 Diabetes by lowering blood sugar levels. The immediate-release form of the medication is Glucophage and the extended-release forms of the medication are Glucophage XR, Fortamet, and Glumetza.

How Does It Work?

In patients suffering from type 2 Diabetes, insulin (the hormone that helps the body remove extra sugar from the blood) naturally produced by the pancreas is unable to get sugar into the body’s cells where it can be properly converted into energy. Metformin, which belongs to a class of drugs known as biguanides, works by reducing the amount of glucose (sugar) made by the liver, decreasing the amount of glucose absorbed by the body, and increasing the impact of naturally produced insulin within the body.

What is NDMA Contamination?

N-nitrosodimethylamine (NDMA) is classified as a probable human carcinogen—meaning that the substance can cause cancer and belongs to class of impurities known as nitrosamines.

NDMA is commonly found in drinking water, some processed foods (pickled vegetables, salted fish, and processed meat products such as bacon and sausages), and as a result of air pollution.

NDMA was once used to make rocket fuel. However, after high levels of NDMA were uncovered in the air, soil, and water samples near manufacturing plants, NDMA use was discontinued. However, NDMA contamination occurs today through unintentional chemical reactions at industrial sites or in the manufacturing process of drugs.

Low levels of NDMA exposure are not dangerous. However, if more than 96 nanograms of NDMA are ingested daily, there is an increased risk of cancer.

Overexposure to NDMA can lead to:

  • Jaundice
  • Fever
  • Vomiting
  • Abdominal cramps
  • Dizziness

Prolonged Exposure to NDMA Contamination can lead to tumors and cancer of the:

  • Liver
  • Stomach
  • Colon & Intestines
  • Esophagus
  • Kidneys
  • Pancreas
  • Bladder

How GoldenbergLaw Can Help You

If you or a loved one contracted cancer after taking a drug recalled due to NDMA contamination, contact the dangerous drug attorneys at GoldenbergLaw. We are committed to promoting safety through accountability and providing you with the gold standard of advocacy.

What You Should Know About The FDA Recall of Zantac

The Food and Drug Administration (FDA) continues to announce recalls of the popular heartburn medication Zantac and its generic formulation ranitidine due to contamination with the known carcinogen N-Nitrosodimethylamine (NDMA). The latest announcements of five additional Zantac and ranitidine recalls come a month after the agency announced initial recalls by Sandoz and Apotex and alerted the public that NDMA had been found in samples of ranitidine. These recalls include both prescription and over-the-counter Zantac.

Do I Have A Case?

Zantac has been on the market for over thirty years and millions of people have taken these medications. For anyone currently taking these drugs, you should immediately contact your doctor to discuss your options.

Zantac Recall Summary

Appco Pharma Ranitidine Recall

On January 8, 2020, Appco Pharma LLC announced a voluntary recall of all lots of its Ranitidine Hydrochloride capsules due to potential NDMA contamination. The recall includes all prescription Ranitidine Hydrochloride capsules in strengths of 150 mg and 300 mg manufactured and distributed by Appco and its marketing partner, ANI Pharmaceuticals.

Northwinds Pharmaceuticals Ranitidine Recall

On January 8, 2020, Denton Pharma, an affiliate of Northwind Pharmaceuticals LLC, voluntarily recalled all lots of prescription Ranitidine 150 mg and 300 mg tablets it had repackaged and distributed at the consumer level.  The recall in is response to the manufacturer’s recall of these medications, which had since been repackaged by Denton Pharma, due to concerns of potential NDMA contamination.

Glenmark Pharmaceuticals Ranitidine Recall

On December 17, 2019, Glenmark Pharmaceuticals Inc. issued a voluntary recall of its unexpired Ranitidine tablet products and halted product distribution due to worries over potential NDMA contamination. In total, 928 lots of Ranitidine 150mg and 300 mg tablets are affected in the recall.

Precision Dose Ranitidine Recall

On November 19, 2019, repackaging company Precision Dose Inc. voluntarily recalled 5 lots of Ranitidine Oral Solution–USP 150mg/ 10mL from the market. The ranitidine product is being recalled due to potential NDMA presence above the standards approved by the Food and Drug Administration.

The recall was initiated after manufacturer Amneal Pharmaceuticals, LLC) issued a voluntary recall which included lots repackaged by Precision Dose Inc.

Golden State Ranitidine Recall

On November 15, 2019, repackaging company Golden State Medical Supply, Incorporated (GSMS, Inc.) voluntarily recalled all quantities and lots of Ranitidine HCl 150mg and 300mg capsules due to the potential presence of NDMA above levels approved by the Food and Drug Administration.

The voluntary recall comes after GSMS, Inc received a recall notice from manufacturer Novitium on October 25, 2019 and initially recalled 7 lots of Ranitidine HCl 150mg and 12 lots of Ranitidine HCl 300mg capsules on November 6, 2019.

American Health Ranitidine Recall

On November 8, 2019, American Health Packaging voluntarily recalled 8 lots of Ranitidine Syrup (Ranitidine Oral Solution USP) 150mg/10mL Liquid Unit Dose Cups from the consumer market due to an “unexpected impurity” of NDMA detected in the finished products at levels deemed unsafe by the Food and Drug Administration.

The recall comes in response to manufacturer Lannett Company, Inc.’s voluntary recall of ranitidine products which included affected lots that were repackaged by American Health Packaging.

Amneal Ranitidine Recall

On November 8, 2019, Amneal Pharmaceuticals, LLC voluntarily recalled Ranitidine Tablets, 150mg and 300mg, and Ranitidine Syrup (Ranitidine Oral Solution, USP), 15mg/mL that were distributed directly to wholesalers, distributors, retailers, and re-packagers due to potential NDMA levels deemed unacceptable by Food and Drug Administration standards.

Lannett Ranitidine Recall

On October 28, 2019 the FDA announced that Lannett Company, Inc. recalled all lots of its prescription ranitidine syrup. The recall includes Lannett’s ranitidine oral solution prescribed in 15mg/mL doses due to the confirmed presence of NDMA.

Novitium Pharma Ranitidine Recall

On October 25, 2019, the FDA confirmed that Novitium Pharma LLC recalled all lots of its over-the-counter Ranitidine Hydrochloride capsules in the United States. Novitium’s ranitidine recall includes all lots of 150 mg and 300 mg dosages sold in 30, 60, 100, and 500 count bottles. The FDA announcement states that the recall was due to potential unsafe levels of NDMA found in the capsules.

Perrigo Ranitidine Recall

On October 23, 2019, the FDA announced that Perrigo Company plc issued a worldwide recall of all lots of its over-the-counter ranitidine products. The announcement states that Perrigo halted shipments of its ranitidine products on October 8 due to the possible presence of NDMA. The Perrigo recall includes many popular ranitidine products, including the Publix over-the-counter store brand.

Dr. Reddy’s Ranitidine Recall

On October 23, 2019, the FDA announced that Dr. Reddy’s Laboratories, LTD. issued a voluntary recall of all lots of its ranitidine products – both prescription and over-the-counter – sold in the United States on October 1. This recall includes lots of ranitidine sold under store brand names at Walgreens, Target, Walmart, Kroger, and CVS. The ranitidine recall was initiated after product testing confirmed unsafe levels of NDMA. For a full list of products recalled under the Dr. Reddy’s ranitidine recall, visit the FDA recall page.

zantac-pill-containersSanofi Zantac OTC Recall

The FDA also confirmed on October 23, 2019 that Sanofi recalled all lots of its Zantac OTC (over-the-counter) medications sold in the United States and Canada on October 18. The company cited “inconsistencies in preliminary test results of the active ingredient used in the U.S. and Canadian products” as the reason for the recall. The Sanofi Zantac OTC recall includes all lots of Zantac 150, Zantac 150 Cool Mint, and Zantac 75.

Apotex Ranitidine Recall

On September 25, 2019, the FDA announced that Apotex Corp. voluntarily recalled its over-the-counter Ranitidine Hydrochloride tablets on a precautionary basis due to concerns of NDMA contamination. The Apotex ranitidine recall applied to 75 mg and 150 mg tablets sold under store brand names at Rite Aid, Walmart, and Walgreens pharmacies.

Sandoz Ranitidine Recall

On September 23, 2019, the FDA announced that Sandoz Inc. recalled all lots of its Ranitidine Hydrochloride capsules sold over-the-counter in the United States due to confirmed NDMA contamination. Sandoz is a subsidiary of the Swiss pharmaceutical conglomerate Novartis. The Sandoz ranitidine recall applies to 14 lots of Ranitidine 150 mg and 300 mg capsules sold in 30, 60, and 500 count bottles.

What Is Zantac?

Zantac is a medication that limits the production of stomach acid and belongs to a class of medications known as H2 blockers. It is sold as a generic under the name of its active ingredient, ranitidine. Zantac is sold over-the-counter to treat heartburn and acid indigestion, and prescribed for the treatment of duodenal and gastric ulcers, gastroesophageal reflux disease, and certain stomach and esophagus conditions.

What Is NDMA?

NDMA is classified as a probable human carcinogen that can form as a byproduct of industrial processes or, as in Zantac, from a reaction with the body. The chemical can be found in small quantities in drinking water but in levels that are considered generally harmless. The NDMA found in the recalled Zantac and ranitidine products is above levels considered safe by the FDA. NDMA had previously been found in the blood pressure medication Valsartan, which prompted a string of product recalls starting in July 2018.

NDMA exposure in Zantac and ranitidine has been linked to digestive system cancers such as:

  • Stomach cancer
  • Intestinal cancer (both of the small and large intestines)
  • Esophageal cancer
  • Prostate cancer
  • Pancreatic cancer
  • Leukemia
  • Non-Hodgkin’s Lymphoma
  • Multiple Myeloma
  • Bladder cancer
  • Stomach cancer
  • Colorectal Cancer
  • Liver Cancer
  • Kidney Cancer

Additionally, in babies born to mothers who took Zantac consistently throughout their pregnancies, NDMA has been linked to cancers, including brain cancers, in young children.

How We Can Help

GoldenbergLaw is currently investigating cases where an individual has taken Zantac or ranitidine and been diagnosed with one of the cancers listed above. Contact our Minnesota cancer attorneys today for a free consultation or call 612-436-5026. We have over 30 years of experience fighting negligent drug companies and have national leadership in NDMA contamination cases, let us deliver the Gold standard you deserve.

NDMA: What Is it and Why Should I Be Concerned?

Many lots of the drug Valsartan were recalled last year due to the contamination of n-nitrosodimethylamine (NDMA), a known animal carcinogen and a probable human carcinogen. More recently, a number of manufacturers recalled their Zantac and ranitidine products due to the belief that the drugs can naturally produce high levels of NDMA as a byproduct of the digestion process.  Many individuals don’t know what NDMA is or how it can impact their health and lifestyle. Here we’ll explore what it is and why the recall was necessary.

Do I Have a Zantac Case?

Do I Have a Valsartan Case?

What Is NDMA?

NDMA is a semi-volatile organic chemical that can form naturally or unintentionally through industrial processes. Unintentional NDMA can form as a byproduct of the chlorination of wastewater and drinking water. This process led NDMA to be found in Valsartan tablets produced by four different facilities:  Zhejiang Huahai Pharmaceuticals in China, Hetero Labs Limited in India, Aurobindo Pharma in India, and Mylan Laboratories, Ltd. in India.

NDMA can also be formed through natural processes. Ranitidine, the active ingredient in Zantac, has a molecular structure that makes it susceptible to naturally creating NDMA once it is ingested. Specifically, the ranitidine compound contains the two elements that are required to form NDMA: nitrite (“N”) and dimethylamine (“DMA”). The presence of both nitrite and dimethylamine in ranitidine’s chemical structure renders it highly capable of producing NDMA under the right conditions.

A recent independent study conducted by Valisure Online Pharmacy sought to understand how capable ranitidine was of naturally producing NDMA. During the testing, Valisure simulated the conditions that ranitidine is exposed to in the human stomach to see how the ranitidine would react; namely, they mixed ranitidine with the gastric fluid and sodium nitrites that stimulate the digestion process. They found that when the ranitidine interacts with the gastric fluid and sodium nitrites found in the stomach, high amounts of NDMA are produced. In fact, when exposed to the simulated stomach conditions, the ranitidine produced approximately 304,500 nanograms (ng) of NDMA per tablet. This is an alarming amount of NDMA, considering the FDA-approved acceptable amount of NDMA intake is 96 ng per day.

Concerns about the molecular generation of NDMA associated with ranitidine have led to several recalls of ranitidine products.

In September 2019, there were voluntary recalls by Sandoz, Inc. and Apotex Corp. The Sandoz ranitidine recall involves 14 lots of prescription capsules, while the Apotex ranitidine recall involves all of its 75mg and 150mg over-the-counter capsules. Many of the Apotex capsules were labeled and sold by popular pharmacies Walgreens, Wal-Mart, and Rite-Aid.

In October 2019, numerous additional voluntary recalls have been announced. On October 23rd, it was announced the Dr. Reddy’s Laboratories Ltd and Sanofi would be recalling ranitidine products. The Dr. Reddy’s recall involves all prescription and over-the-counter capsules manufactured by the company, while Sanofi issued a recall of its over-the-counter ranitidine. On October 28th, it was announced that Perrigo Company, Novitium Pharma LLC, and Lannett Company, Inc. would be recalling ranitidine products as well due to the presence of NDMA. Perrigo Company is recalling all over-the- counter ranitidine tablets; Novitium Pharma is recalling all ranitidine hydrochloride capsules; and, the Lannett Company recall involves all lots of prescription ranitidine syrup.

While several recalls have already occurred, several other countries, including Canada, have taken further action by ordering complete recalls of all Zantac and ranitidine products.

In December 2019, the regulators for multiple global health organizations began testing samples of the type 2 diabetes drug metformin for NDMA contamination. As of December 5, 2019, there has been no metformin recall in the United States. The FDA said in a statement that it has not confirmed any NDMA contamination of metformin sold in the United States, but that any contamination detected beyond the acceptable daily intake limit will lead to recommended recalls. Singapore’s Health Sciences Authority announced on December 4 that is was recalling three metformin medications due NDMA contamination.

Metformin is manufactured as a generic by multiple global pharmaceutical companies. Popular brand name drugs sold in the United States that contain metformin include Fortamet, Glucophage, Glucophage XR, Glumetza, and Riomet.

What Are the Effects?

NDMA can contaminate drinking water and humans often get NDMA exposure from consuming food or drink that was contaminated with NDMA. Exposure to NDMA in Valsartan can cause prostate cancer, lower esophageal cancer, non-hodgkins lymphoma, leukemia, multiple myeloma, colon, stomach, intestinal, or pancreatic cancer. Even small amounts of exposure can lead to liver damage. Exposure to NDMA in ranitidine has been linked to a number of cancers including stomach cancer, cancer in the small and large intestines, colorectal cancer, esophageal cancer, kidney cancer, bladder cancer, liver cancer, prostate cancer, pancreatic cancer, leukemia, non-hodgkin’s lymphoma, and multiple myeloma.

Classified as a Carcinogen

The EPA classifies NDMA as a B2 carcinogen, meaning it is a probable human carcinogen. B2 carcinogens do not have enough human data but have a sufficient amount of animal data to conclude that it’s a potential carcinogen. Many animal studies were done to test NDMA, and they found that various species, including rats and mice, developed tumors in the liver, respiratory tract, and blood vessels after exposure to NDMA. The U.S. Department of Health and Human Services believes that NDMA is “reasonably anticipated to be a human carcinogen.”

Contact GoldenbergLaw

If you or a loved one contracted cancer after taking Valsartan, ranitidine, or metformin, contact the dangerous drug attorneys at GoldenbergLaw. We are committed to promoting safety through accountability.